{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:14:18Z","timestamp":1790187258340,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014598","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000}}],"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["RO1EY024649"],"award-info":[{"award-number":["RO1EY024649"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["RO1EY033574"],"award-info":[{"award-number":["RO1EY033574"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["RO1EY029160"],"award-info":[{"award-number":["RO1EY029160"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Macrophages play multifaceted and critical roles in controlling diverse pathogenic infections. Building on our recently published observations of macrophages exhibiting memory responses to HSV-1 infection, our current report investigates the macrophage subtype responsible for generating trained immunity against virus-induced immunopathogenesis. Using ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing), an epigenetic profiling technique, we identified chromatin accessibility changes in both M1 and M2 macrophages associated with the acquisition of IRGM1, a marker of the trained phenotype. To conduct this study, we first generated M0, M1, and M2 macrophage subtypes from bone marrow (BM) derived macrophages isolated from HSV-1 latently infected wild type (WT) mice. ATAC-seq revealed that M1-generated macrophages displayed higher IRGM1-associated chromatin accessibility peaks compared to M2 and M0 subtypes, and this response was enhanced after stimulation with UV-inactivated virus. To further dissect this response, we analyzed memory responses in bone marrow-derived macrophages, spleen macrophages, corneal macrophages, and trigeminal ganglia (TG) of latently infected M1 and M2 macrophages. Flow cytometry and ATAC-seq data showed a significantly higher proportion of IRGM1\u2009\u207a\u2009macrophages in infected M2\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice, which are enriched in M1 macrophages. These findings indicate that M1 macrophages, but not M2 macrophages, undergo trained immunity in response to HSV-1 infection. This is also confirmed by the Luminex assay, in which M1 macrophages, after stimulation, then known as primed M1 macrophages, enhance the secretion of pro-inflammatory cytokine\/chemokine response to secondary HSV-1 exposure. These results uncover a previously underappreciated role for macrophage-mediated trained immunity in antiviral defense against HSV-1 infection and offer new insights into potential therapeutic targets for modulating host immune responses during HSV-1 infection.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014598","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:43:15Z","timestamp":1788975795000},"page":"e1014598","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epigenetic profiling reveals M1 macrophages as the primary drivers of trained immunity in HSV-1 latently infected mice"],"prefix":"10.1371","volume":"22","author":[{"given":"Ujjaldeep","family":"Jaggi","sequence":"first","affiliation":[{"name":"Center for Neurobiology & Vaccine Development, Cedars-Sinai Health Sciences University, Ophthalmology Research","place":["Los Angeles, California, United States of America"],"department":["Department of Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohui","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Neurobiology & Vaccine Development, Cedars-Sinai Health Sciences University, Ophthalmology Research","place":["Los Angeles, California, United States of America"],"department":["Department of Surgery"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3291-1995","authenticated-orcid":true,"given":"Homayon","family":"Ghiasi","sequence":"additional","affiliation":[{"name":"Center for Neurobiology & Vaccine Development, Cedars-Sinai Health Sciences University, Ophthalmology Research","place":["Los Angeles, California, United States of America"],"department":["Department of 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